The goal of this proposal is to perfect and apply a proteomic approach to supplement ongoing attempts (P01-AG022550-01) to determine the mechanisms responsible for age-related decrements in brain function. A significant body of evidence supports the hypothesis that oxidative stress may be a causal factor in such age-related changes. In this proposal, we will identify the specific protein targets of oxidation in the aging mouse brain and determine which of them are related to the severity of the age-associated attenuations in cognitive function. The main experimental design of this study w ill entail scoring groups of aged and young mice on a specific cognitive task (Morris water maze). The degree of association will be determined between performance in the cognitive task and the degree of oxidation, measured as carbonylation, associated with individual proteins in different regions of the brain. The specific brain regions and subcellular fractions to be targeted for identification of the aging-associated oxidation-sensitive proteins (AOSPs) will be those showing age-associated oxidative stress as measured by various other parameters described in Project 1 of AG022550. A positive correlation between the degree of loss in a specific cognitive or psychomotor domain and an AOSP will suggest a functional involvement of the protein in brain aging. Moreover, the identity of the AOSP will provide highly specific and testable hypotheses about the causes of age-associated functional decline. [unreadable] [unreadable]